Displaying publications 1 - 20 of 142 in total

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  1. Ghazali MM, Mohd Zan MS, Yusof AA, Abdullah JM, Jaffar H, Ariff AR, et al.
    Malays J Med Sci, 2005 Jul;12(2):27-33.
    PMID: 22605955 MyJurnal
    Neoplastic transformation appears to be a multi-step process in which the normal controls of cell proliferation and cell-cell interaction are lost, thus transforming normal cells into cancer. The tumorigenic process involves the interplay between oncogenes and tumour suppressor genes. In this study, we have selected the ras family, c-myc and epidermal growth factor receptor (EGFR) genes to detect whether their abnormalities are associated with the expression and progression of glioma cases in Malay patients. We have used the polymerase chain reaction-single stranded conformation polymorphism followed by direct sequencing for the study. For the ras gene family, we screened the point mutations in codons 12 and 61 of the H-, K-, and N-ras gene; for EGFR and c-myc, we analyzed only the exon 1 in glioma samples. In mutational screening analyses of the ras family, c-myc and EGFR gene, there was no mobility shift observed in any tumour analyzed. All patterns of single stranded conformation polymorphism (SSCP) band observed in tumour samples were normal compared to those in normal samples. The DNA sequencing results in all high-grade tumours showed that all base sequences were normal. All 48 patients survived after five years of treatment. In simple logistic regression analysis, variables which were found to be significant were hemiplegia (p=0.047) and response radiotherapy (p=0.003). Hemiplegics were 25 times more likely to have high pathological grade compared to those without. Patients with vascular involvement were 5.5 times more likely to have higher pathological grade. However, these findings were not significant in multivariate analysis. Patients who had radiotherapy were nearly 14 times more likely to have higher pathological grade. Multivariate analysis revealed that patients with hemiplegia were more likely to have higher pathological grade (p= 0.008). Those with higher pathological grading were 80 times more likely to have radiotherapy (p=0.004).
  2. Das S, Haji Suhaimi F, Abd Latiff A, Pa Pa Hlaing K, Abd Ghafar N, Othman F
    Rom J Morphol Embryol, 2009;50(3):509-11.
    PMID: 19690784
    Peroneus tertius (PT) is a muscle of the anterior compartment of the leg. The PT muscle originates from the anterior surface of the fibula and the interosseous membrane and inserts into the medial side of the dorsal region of the fifth metatarsal bone. During routine dissection, we observed the absence of PT on the left lower limb of a cadaver. Usually, the PT is involved in dorsiflexion and eversion of the foot. In many cases, the absence of PT maybe asymptomatic and it may be incidentally detected during cadaveric dissections or autopsies. The existence of PT may help in the swing phase of bipedal walking. The PT may be used for tendon graft surgeries. The pull of the PT may be responsible for causing stress on the fifth metacarpal and account for all stress fractures in any individual. The absence of the PT may puzzle any transplant and foot surgeons performing graft operations. We as anatomists discuss the clinical implications of the absence of PT.
  3. Hlaing KP, Das S, Sulaiman IM, Abd-Latiff A, Abd-Ghafar N, Suhaimi FH, et al.
    Bratisl Lek Listy, 2010;111(5):308-10.
    PMID: 20568426
    The renal artery is known to exhibit variations in its number and position. The present study was performed on 50 cadaveric kidneys to observe the topographical anatomy of the accessory renal arteries (ARA) entering the upper or lower poles of the kidney. Out of 50 kidney cadaveric specimens (irrespective of sex) studied, 2 kidneys (4%) showed the presence of ARA. The presence of ARA was observed on the left and right kidneys, respectively. In one left kidney, we observed in addition to the usual renal artery, an ARA near the lower pole of the kidney which divided into anterior and posterior branches. Another right kidney specimen exhibited the presence of single and double ARA at the upper and the lower poles, respectively. The presence of ARA, both at the upper and lower poles is a rare entity. No medical history of the cadavers was available to corroborate the clinical findings. Additional renal vessels may signify a developmental defect. Anatomical knowledge of the variations in the renal vascular supply may be important for abdominal imaging studies and surgical operations involving renal transplantations. The present study discusses in detail the anatomical features and clinical implications of ARA located at both the upper and lower poles of the kidney (Fig. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.
  4. Jafarlou M, Baradaran B, Saedi TA, Jafarlou V, Shanehbandi D, Maralani M, et al.
    J Biol Regul Homeost Agents, 2016 Apr-Jun;30(2):315-21.
    PMID: 27358116
    Gene therapy has become a significant issue in science-related news. The principal concept of gene therapy is an experimental technique that uses genes to treat or prevent disease. Although gene therapy was originally conceived as a way to treat life-threatening disorders (inborn defects, cancers) refractory to conventional treatment, it is now considered for many non–life-threatening conditions, such as those adversely impacting a patient’s quality of life. An extensive range of efficacious vectors, delivery techniques, and approaches for developing gene-based interventions for diseases have evolved in the last decade. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. The aim of this review is to investigate the general methods by which genes are transferred and to give an overview to clinical applications. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, and a high safety profile. Gene therapy has made substantial progress albeit much slower than was initially predicted. This review also describes the basic science associated with many gene therapy vectors and the present progress of gene therapy carried out for various surface disorders and diseases. The conclusion is that, with increased pathobiological understanding and biotechnological improvements, gene therapy will become a standard part of clinical practice.
  5. Omar AR, Ideris A, Ali AM, Othman F, Yusoff K, Abdullah JM, et al.
    Malays J Med Sci, 2003 Jan;10(1):4-12.
    PMID: 23365495
    Newcastle disease virus (NDV) is one of the most economically important avian virus which affects the poultry industry worldwide. Although NDV is being very actively studied in Malaysia, there are still no studies on its potential as an anticancer agent, a new approach to treating cancer known as virotherapy. Currently, a collaborative research is being undertaken between Universiti Putra Malaysia (UPM), Universiti Sains Malaysia (USM) and Majlis Kanser Nasional (MAKNA) in characterising various local NDV isolates as anticancer agent. This paper describes an overview of the research that have been carried out worldwide in the use of NDV for cancer treatment and also some of our findings in characterising local NDVs with oncolytic properties.
  6. Das S, Maatoq Sulaiman I, Hussan F, Haji Suhaimi F, Latiff AA, Othman F
    Clin Ter, 2009;160(1):25-7.
    PMID: 19290409
    The flexor compartment muscles of the arm comprising of biceps brachii, brachialis and the coracobrachialis are innervated by the musculocutaneous nerve arising from the lateral cord of the brachial plexus. In the present study, we report a case of anomalous innervation of the corachobrachialis muscle on the left side of a 45-year-old male cadaver. The musculocutaneous nerve originated from the lateral cord, as usual and pierced the corachobrachialis muscle. The median nerve was formed by a contribution from both lateral and medial roots, both of which took origin from the lateral and medial cords, respectively. In addition to the usual musculocutaneous nerve which pierced the corachobrachialis muscle and innervated it, two more anomalous branches from the median nerve were observed to innervate the corachobrachialis. The anatomical knowledge of the variations of the innervations of the corachobrachialis muscle may be important not only for surgeons performing coracoid transfer but also for clinicians diagnosing nerve lesions.
  7. Ansari M, Othman F, Abunama T, El-Shafie A
    Environ Sci Pollut Res Int, 2018 Apr;25(12):12139-12149.
    PMID: 29455350 DOI: 10.1007/s11356-018-1438-z
    The function of a sewage treatment plant is to treat the sewage to acceptable standards before being discharged into the receiving waters. To design and operate such plants, it is necessary to measure and predict the influent flow rate. In this research, the influent flow rate of a sewage treatment plant (STP) was modelled and predicted by autoregressive integrated moving average (ARIMA), nonlinear autoregressive network (NAR) and support vector machine (SVM) regression time series algorithms. To evaluate the models' accuracy, the root mean square error (RMSE) and coefficient of determination (R2) were calculated as initial assessment measures, while relative error (RE), peak flow criterion (PFC) and low flow criterion (LFC) were calculated as final evaluation measures to demonstrate the detailed accuracy of the selected models. An integrated model was developed based on the individual models' prediction ability for low, average and peak flow. An initial assessment of the results showed that the ARIMA model was the least accurate and the NAR model was the most accurate. The RE results also prove that the SVM model's frequency of errors above 10% or below - 10% was greater than the NAR model's. The influent was also forecasted up to 44 weeks ahead by both models. The graphical results indicate that the NAR model made better predictions than the SVM model. The final evaluation of NAR and SVM demonstrated that SVM made better predictions at peak flow and NAR fit well for low and average inflow ranges. The integrated model developed includes the NAR model for low and average influent and the SVM model for peak inflow.
  8. Pishva SR, Vasudevan R, Etemad A, Heidari F, Komara M, Ismail P, et al.
    Int J Mol Sci, 2013 Jan 28;14(2):2739-52.
    PMID: 23358257 DOI: 10.3390/ijms14022739
    Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects.
  9. Naomi R, Teoh SH, Embong H, Balan SS, Othman F, Mamat-Hamidi K, et al.
    Foods, 2023 Sep 26;12(19).
    PMID: 37835227 DOI: 10.3390/foods12193575
    Maternal obesity, characterized by an elevated body mass index (BMI) during pregnancy, is known to have adverse effects on the offspring. However, a recent study suggests that Elateriospermum tapos (E. tapos) yogurt may hold potential in mitigating excessive weight retention post-pregnancy. Thus, this study aims to employ network pharmacology to explore the pharmacological effects of the bioactive compounds present in E. tapos yogurt against maternal obesity. Initially, a screening process is conducted to identify the bioactive compounds in E. tapos yogurt, followed by the prediction of potential gene targets for these compounds using Swiss Target Prediction and the SuperPred databases. Maternal obesity-associated genes are sourced from the OMIM, DisGeNet, and GeneCards databases. The interaction between the identified compounds and maternal obesity genes is established via protein-protein interaction analysis, gene ontology examination, and KEGG pathway analysis. To validate the results, molecular docking studies are conducted using AutoDock Tools software. The findings reveal that out of the 64 compounds analyzed, three meet the screening criteria, resulting in a total of 380 potential gene targets. Among these targets, 240 are shared with maternal obesity-related genes. Further analysis demonstrates the favorable affinity of these active compounds with key targets, linking them to biological processes involving protein phosphorylation, inflammation, as well as the pathways related to lipid metabolism, atherosclerosis, and the other signaling pathways. In conclusion, this study provides valuable insights into the potential pharmacological effects of the bioactive compounds found in E. tapos yogurt against maternal obesity. These findings open avenues for further exploration and potential therapeutic interventions targeting maternal obesity.
  10. Fathi M, Cheah PS, Ahmad U, Nasir MN, San AA, Abdul Rahim E, et al.
    Biomed Res Int, 2017;2017:6307019.
    PMID: 28484716 DOI: 10.1155/2017/6307019
    Ethnic origin plays an important role in bone morphometry. Studies examining the influence of coracoid process have focused primarily on adults and have not included people from diverse Asian ethnic backgrounds. Our goal was to explore ethnic differences in morphometry of coracoid among Asian population. We performed morphometric measurements of coracoid process on cadaveric shoulders and shoulder CT scans from 118 specimens. The cadaveric sample included Indian (46%), Chinese (27%), and Myanmarese (27%) subjects, while the CT scans sample included Chinese (67%) and Malay (33%) subjects. The morphometric measurements were performed using digital caliper and software developed at Golden Horses Health Sanctuary (GHHS). In the Indian cadaveric shoulders, the coracoid process is better developed than the other groups with the exception of the tip width of coracoid process. There are significant differences in almost all measurements (P< 0.05) between the ethnic groups. On the other hand, the morphometry of coracoid process from CT scans data is bigger in Chinese than Malay subjects when stratified by sex (P< 0.05). Moreover, in all morphometric measurements, the females had smaller measurements than males (P< 0.05). Understanding such differences is important in anatomy, forensic and biological identity, and orthopaedic and shoulder surgeries.
  11. Das S, Abd Latiff A, Suhaimi FH, Ghazalli H, Othman F
    Bratisl Lek Listy, 2008;109(11):513-6.
    PMID: 19205563
    To study the anomalous splenic notches and discuss their clinical importance.
  12. Das S, Suhaimi FH, Othman F, Latiff AA
    Bratisl Lek Listy, 2008;109(1):31-3.
    PMID: 18447260
    In literature, there is paucity of information on the different shapes of styloid processes of the temporal bone of the skull. Textbooks of anatomy describe the styloid process to be slender, approximately 2.5 cm in length and concave on the anterior aspect only. In the present case, we observed the styloid process to be much longer than usual, bearing a concavity on the anterior, as well as the posterior aspects as a consequence of which, the bone was constricted in its proximal part. The mastoid process which is usually conical, was found to be rounded in this case. The length of the styloid process measured 2.8 and 2.7 cm on left and right sides, respectively. The skiagram displayed the biconcave profile of the styloid process and the rounded appearance of the mastoid process, thus substantiated the findings on gross examination of the skull. The anatomical knowledge of the mastoid process is important for surgeons assessing the mastoid air cells. The elongated styloid process is often a feature of Eagle's syndrome. An enlarged and calcified styloid process is often asymptomatic, unless detected radiologically. An abnormally elongated styloid process or its calcification may cause recurrent throat pain, foreign body sensation, dysphagia, or facial pain. An enlarged styloid process may also compress upon the internal carotid artery, leading to transient ischemic attack and may pose a threat to anesthetists performing intubation procedures. Awareness of such variations may be of clinical importance to radiologists and surgeons (Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.
  13. Hussan F, Mansor AS, Hassan SN, Tengku Nor Effendy Kamaruddin TN, Budin SB, Othman F
    PMID: 26300946 DOI: 10.1155/2015/347861
    Hepatic injury induces inflammatory process and cell necrosis. Plantago major is traditionally used for various diseases. This study aimed to determine the anti-inflammatory property of P. major leaf extracts on inflammatory reaction following acetaminophen (APAP) hepatotoxicity. Thirty male Sprague-Dawley rats were divided into 5 groups, namely, normal control (C), APAP, aqueous (APAP + AQ), methanol (APAP + MT), and ethanol (APAP + ET) extract treated groups. All APAP groups received oral APAP (2 g/kg) at day 0. Then, 1000 mg/kg dose of P. major extracts was given for six days. The levels of liver transaminases were measured at day 1 and day 7 after APAP induction. At day 7, the blood and liver tissue were collected to determine plasma cytokines and tissue 11β-HSD type 1 enzyme. The in vitro anti-inflammatory activities of methanol, ethanol, and aqueous extracts were 26.74 ± 1.6%, 21.69 ± 2.81%, and 12.23 ± 3.15%, respectively. The ALT and AST levels were significantly higher in the APAP groups at day 1 whereas the enzyme levels of all groups showed no significant difference at day 7. The extracts treatment significantly reduced the proinflammatory cytokine levels and significantly increased the 11β-HSD type 1 enzyme activity (p < 0.05). In conclusion, the P. major extracts attenuate the inflammatory reaction following APAP-induced liver injury.
  14. Hamid RA, Kee TH, Othman F
    Pharmacognosy Res, 2013 Apr;5(2):129-33.
    PMID: 23798889 DOI: 10.4103/0974-8490.110544
    Acanthopanax trifoliatus is a ginseng-like plant, which has been widely used to treat various diseases including inflammatory-related diseases.
  15. Sulaiman H, Hamid RA, Ting YL, Othman F
    J Cancer Res Ther, 2012 Jul-Sep;8(3):404-10.
    PMID: 23174723 DOI: 10.4103/0973-1482.103521
    CONTEXT: Ardisia crispa Thunb. A. DC (Myrsinaceae) or locally known as hen's eyes has been used in local folk medicine as a remedy in various illnesses. Previously, it has been reported to inhibit various inflammatory diseases. However, research done on this plant is still limited.
    AIMS: In the present study, the hexane fraction of the A. crispa root (ACRH) was evaluated on the peri-initiation and promotion phases of skin carcinogenesis.
    MATERIALS AND METHODS: This two-stage skin carcinogenesis was induced by a single topical application of 7,12-dimethylbenz(α)anthracene (DMBA) and promoted by repeated treatment with croton oil for 10 weeks in Imprinting Control Region (ICR) mice. Morphological observation would be conducted to measure tumor incidence, tumor burden, and tumor volume. Histological evaluation on the skin tissue would also be done.
    RESULTS: The carcinogen control group exhibited 66.67% of tumor incidence. Although, in the ACRH-treated groups, at 30 mg/kg, the mice showed only 10% of tumor incidence with a significant reduction (P < 0.05) in the values of tumor burden and tumor volume of 2.00 and 0.52 mm(3), respectively. Furthermore, the result was significantly lower than that of the carcinogen and curcumin control. At 100 mg/kg, ACRH showed a comparable result to carcinogen control. On the contrary, at 300 mg/kg, ACRH exhibited 100% tumor incidence and showed a significant elevated (P < 0.05) value of tumor burden (3.80) and tumor volume (14.67 ± 2.48 mm(3)).
    CONCLUSIONS: The present study thus demonstrates that the anti-tumor effect of the chemopreventive potential of ACRH is at a lower dosage (30 mg/kg bwt) in both the initiating and promotion period, yet it exhibits a promoting effect at a higher dosage (300 mg/kg bwt).
  16. Md Nasir NL, Kamsani NE, Mohtarrudin N, Othman F, Md Tohid SF, Zakaria ZA
    Pharm Biol, 2017 Dec;55(1):2102-2109.
    PMID: 28872373 DOI: 10.1080/13880209.2017.1371769
    CONTEXT: Leaves of Muntingia calabura (Elaeocarpaceae) are widely used in traditional medical practice; scientific findings show various pharmacological activities. However, its anticancer effect has not been investigated thoroughly yet.

    OBJECTIVE: The objective of this study is to study the chemoprevention effects of MEMCL against azoxymethane (AOM)-induced colon cancer and to examine the involvement of endogenous antioxidants Materials and methods: Male Sprague-Dawley rats, divided into five groups (n = 7), were injected intraperitoneally once weekly for 2 weeks with 15 mg/kg AOM, except for the normal group (received saline). The animals were then administered orally for 8 weeks with 8% Tween-80 (vehicle; normal group), 8% Tween-80 (vehicle; cancer group) or, 50, 250 or 500 mg/kg MEMC. After treatments, colon samples were collected from each rat for the histopathological analysis, quantification of aberrant crypt foci formed and determination of colon antioxidant levels. MEMC was also subjected to HPLC analysis.

    RESULTS: The extract exerted significant (p 

  17. Zakaria ZA, Abdul Rahim MH, Roosli RAJ, Mohd Sani MH, Omar MH, Mohd Tohid SF, et al.
    Pain Res Manag, 2018;2018:9536406.
    PMID: 29686743 DOI: 10.1155/2018/9536406
    Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic-signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.
  18. Aboonabi A, Rahmat A, Othman F
    Toxicol Rep, 2014;1:915-922.
    PMID: 28962304 DOI: 10.1016/j.toxrep.2014.10.022
    Oxidative stress attributes a crucial role in chronic complication of diabetes. The aim of this study was to determine the most effective part of pomegranate on oxidative stress markers and antioxidant enzyme activities against streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Male Sprague-Dawley rats were randomly divided into six groups. Experimental diabetes was induced by a single intraperitoneal injection (i.p), 15 min after the i.p administration of NA. Diabetic rats showed significant increase in plasma glucose level, and the significant decrease in plasma insulin level. The activities of antioxidant enzymes such as total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) reduced while the levels of biomarkers of oxidative stress such as gamma-glutamyle transferase (GGT), and malondialdehyde (MDA) increased in diabetic control rats as compared to normal control rats. Oral treatment with pomegranate seed-juice for 21 days demonstrated significant protective effects on all the biochemical parameters studied. Besides, biochemical findings were supported by histopathological study. These results revealed that pomegranate has potential protective effect against oxidative stress induced diabetic rats.
  19. Wan Mohd Zain WN, Rahmat A, Othman F, Yap TY
    Malays J Med Sci, 2009 Jul;16(3):29-34.
    PMID: 22589662 MyJurnal
    CLAUSINE B, A CARBAZOLE ALKALOID ISOLATED FROM THE STEM BARK OF CLAUSENA EXCAVATA, WAS INVESTIGATED FOR ITS ANTIPROLIFERATIVE ACTIVITIES AGAINST FIVE HUMAN CANCER CELL LINES: HepG2 (hepatic cancer), MCF-7 (hormone-dependent breast cancer), MDA-MB-231 (non-hormone-dependent breast cancer), HeLa (cervical cancer), and CAOV3 (ovarian cancer).
  20. Lope Pihie AH, Zakaria ZA, Othman F
    PMID: 22474490 DOI: 10.1155/2012/123470
    The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway.
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